The objective of this proposal is to determine the role of calcium ions in the mechanism of gonadotropin releasing hormone (GnRH)-stimulated release of luteinizing hormone (LH) from the pituitary. This objective will be attained by analysis and manipulation of calcium movement, localization of calcium binding and contractile proteins, blockage and activation of calcium target proteins, direct measurement of cellular calcium potentials, and determination of specific sites of calcium action in response to stimulation by GnRH in pituicytes. The present proposal developed from studies by us and other laboratories which showed that LH release in pituicytes was not mediated by a cyclic AMP-dependent mechanism. We subsequently developed a line of evidence which implicated calcium in the mechanism of GnRH-induced LH release. The present proposal seeks to pursue these observations and will lead to the elucidation of the specific role of calcium in this release process. Determination of the precise mechanism by which GnRH mediates its action will increase our understanding of control of the hypothalamic-pituitary-gonadal axis and therefore will be useful in understanding and correcting diseases of gonadotropic dysfunction as well as in regulation of fertility, reproductive function and secondary sex characteristics.